Post-biopsy cavity treatment implants and methods

ABSTRACT

A method of treating a cavity created by a percutaneous excisional procedure carried out through an incision includes steps of providing a post-procedure cavity implant, the post-procedure cavity implant including: a radiopaque element; a core portion coupled to the radiopaque element, the core portion including a first porous matrix defining a first controlled pore architecture, and a shell portion coupled to the core portion, the shell portion including a second porous matrix defining a second controlled pore architecture that is different from the first controlled pore architecture; implanting the post-procedure cavity implant into the cavity, and closing the incision.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 10/688,289,filed Oct. 16, 2003, which application is hereby incorporated herein byreference in its entirety and from which priority is hereby claimedunder 35 U.S.C. §120. This application is related in subject matter toapplication Ser. No. 10/627,960, filed Jul. 25, 2003.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to post-biopsy cavity treatment methodsand implants. More particularly, the present invention relates topost-biopsy cavity treatment implants inserted into cavities formed insoft tissue that may be created during a biopsy or therapeuticexcisional procedure.

2. Description of the Related Art

Breast biopsies are routinely performed in the United States following adetection of abnormalities discovered through mammographicvisualization, manual palpation or ultrasound examination. There are anumber of traditional methods to obtain breast biopsy tissue samples,including surgical excisional biopsies and stereotactic and ultrasoundguided needle breast biopsies. Recently, methodologies have emerged thatare based upon percutaneous minimally invasive large intact tissuesample collection. The use of these devices results in a unique cavityconnected to the skin by a narrow neck. For example, such cavities maygenerally resemble an igloo. It is becoming apparent that thepost-biopsy cavities left within the patient by such procedures maybenefit from different post procedure treatment methods and implants, ascompared to the post-procedure treatment methods and implants (if any)conventionally employed to treat cavities left by needle, core biopsyprocedures or open surgical procedures. In part, this need for newpost-procedure methods and implants is driven by the different nature,size and shape of the cavity created by such emerging percutaneousminimally invasive large intact tissue sample collection methods anddevices.

In certain cases, locating a previously biopsied area is highlydesirable. Therefore, to mark the biopsy site, a variety of biopsy sitemarkers and identifiers have been developed, ranging from metal clips topellets and sponges placed during or right after the biopsy procedure.Usually, these markers contain radiopaque and/or echogenic articles andinclude features such as metal clips and air or gas bubbles incorporatedin a biodegradable matrix. However, existing markers are believed to beunsuited to the unique size and shape of some cavities, in that they donot adequately fill the cavity, do not adequately promote tissueingrowth, and are not easily visualizable, among other disadvantages. Ithas become apparent, therefore, that new post-biopsy and post-procedurecavity implants and treatment methods are needed that are better suitedto the percutaneous minimally invasive large intact tissue samplecollection methods and devices that are currently gaining favor in themedical community.

SUMMARY OF THE INVENTION

The present invention, according to an embodiment thereof, is a methodof treating a cavity created by a percutaneous excisional procedurecarried out through an incision. The method may include steps ofproviding a post-procedure cavity implant, the post-procedure cavityimplant including: a radiopaque element; a core portion coupled to theradiopaque element, the core portion including a first porous matrixdefining a first controlled pore architecture, and a shell portioncoupled to the core portion, the shell portion including a second porousmatrix defining a second controlled pore architecture that is differentfrom the first controlled pore architecture; implanting thepost-procedure cavity implant into the cavity, and closing the incision.

The core portion may surround the radiopaque element. The shell portionmay surround the core portion. Alternatively still, the core portion maysurround the radiopaque element and the shell portion may surround thecore portion. The core and/or the shell portions may include one or moreradioactive materials.

The shell portion may swell faster than the core portion when theimplant is placed in a biological fluid environment (or other aqueousenvironment). The shell portion may swell to a greater extent than thecore portion when the implant is placed in the biological fluidenvironment. The first controlled pore architecture may differ from thesecond controlled pore architecture with respect to at least one of:pore density, pore shape, pore orientation and/or pore dimensions. Theradiopaque element may include a portion having a paramagnetic property.The core and/or shell portions may include a dye disposed therein, whichmay be radioactive. The core and/or shell portions may include a pigmentdisposed therein, which may be radioactive. The core and/or shellportions may include a contrast medium disposed therein. The core and/orshell portions may include a therapeutic agent disposed therein. Thecore and/or shell portions may be biodegradable. At least the shellportion may include collagen. The core portion may include a polylactide(PLA), a polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), apolyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipid, apolysaccharide, a starch and/or a polyorthoester, for example. The coreand shell portions may be configured so as to form a laminar structure.The core or the shell portion may be echogenic. At least the shellportion may include a plurality of fibers. The core and/or shellportions may include an internal reservoir configured to contain a dye,a pigment and/or a therapeutic agent, for example. The internalreservoir may be configured to deliver the dye, pigment and/ortherapeutic agent through elution when the implant is placed (e.g.,implanted) in a biological fluid environment. The internal reservoir maybe configured to deliver the dye, pigment and/or therapeutic agent at afirst rate when the reservoir is breached and at a second rate that islower than the first rate when the reservoir is not breached. The shellportion may be configured to swell to a greater degree than the coreportion when the implant is placed in the biological fluid environment.The shell portion may include collagen and a crosslinking density of theshell portion may be controlled through adding a selected amount of abifunctional reagent to the collagen. The bifunctional reagent mayinclude, for example, an aldehyde and/or a cyanamide. The aldehyde mayinclude a glutaraldehyde, for example. The shell portion may includecollagen and a crosslinking density of the shell portion may becontrolled by an application of energy to the collagen. The applicationof energy may include dehydrothermal processing, exposure to UV lightand/or radiation, for example. The shell portion may include collagenand a crosslinking density of the shell portion may be controlled by acombination of dehydrothermal processing and exposure to cyanamide, forexample. The implant, in a state prior to being placed in a biologicalfluid environment, may be generally wedge-shaped. The implant, in astate prior to being placed in a biological fluid environment (e.g., ina pre-implantation state), may have a rectangular shape or the shape ofa disk that may have been folded multiple times. The shell portion maydefine a center portion and a peripheral portion and the peripheralportion may be configured to define a plurality of independently movablefree ends. The core portion and/or the shell portion may include aradioactive material.

According to another embodiment thereof, the present invention is also amethod of treating a cavity created by an excisional procedure. Themethod may include steps of selecting a first biodegradation rate range;selecting a second biodegradation rate range that is different from thefirst biodegradation rate range; providing a post-procedure cavityimplant, the post-procedure cavity implant including: a radiopaqueelement; a core portion coupled to the radiopaque element, the coreportion being configured to biodegrade at a first effective rate withinthe first biodegradation rate range, and a shell portion coupled to thecore portion, the shell portion being configured to biodegrade at asecond effective rate within the second biodegradation rate range, andimplanting the post-procedure cavity implant within the cavity.

The shell portion may swell faster than the core portion when theimplant is placed in a biological fluid environment (or other aqueousenvironment). The shell portion may swell to a greater extent than thecore portion when the implant is placed in the biological fluidenvironment. The first controlled pore architecture may differ from thesecond controlled pore architecture with respect to at least one of:pore density, pore shape, pore orientation and/or pore dimensions. Theradiopaque element may include a portion having a paramagnetic property.The core and/or shell portions may include a dye disposed therein, whichmay be radioactive. The core and/or shell portions may include a pigmentdisposed therein, which may be radioactive. The core and/or shellportions may include a contrast medium disposed therein. The core and/orshell portions may include a therapeutic agent disposed therein. Thecore and/or shell portions may be biodegradable. At least the shellportion may include collagen. The core portion may include a polylactide(PLA), a polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), apolyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipid, apolysaccharide, a starch and/or a polyorthoester, for example. The coreand shell portions may be configured so as to form a laminar structure.The core or the shell portion may be echogenic. At least the shellportion may include a plurality of fibers. The core and/or shellportions may include an internal reservoir configured to contain a dye,a pigment and/or a therapeutic agent, for example. The internalreservoir may be configured to deliver the dye, pigment and/ortherapeutic agent through elution when the implant is placed (e.g.,implanted) in a biological fluid environment. The internal reservoir maybe configured to deliver the dye, pigment and/or therapeutic agent at afirst rate when the reservoir is breached and at a second rate that islower than the first rate when the reservoir is not breached. The shellportion may be configured to swell to a greater degree than the coreportion when the implant is placed in the biological fluid environment.The shell portion may include collagen and a crosslinking density of theshell portion may be controlled through adding a selected amount of abifunctional reagent to the collagen. The bifunctional reagent mayinclude, for example, an aldehyde and/or a cyanamide. The aldehyde mayinclude a glutaraldehyde, for example. The shell portion may includecollagen and a crosslinking density of the shell portion may becontrolled by an application of energy to the collagen. The applicationof energy may include dehydrothermal processing, exposure to UV lightand/or radiation, for example. The shell portion may include collagenand a crosslinking density of the shell portion may be controlled by acombination of dehydrothermal processing and exposure to cyanamide, forexample. The implant, in a state prior to being placed in a biologicalfluid environment, may be generally wedge-shaped. The implant, in astate prior to being placed in a biological fluid environment (e.g., ina pre-implantation state), may have a rectangular shape or the shape ofa disk that may have been folded multiple times. The shell portion maydefine a center portion and a peripheral portion and the peripheralportion may be configured to define a plurality of independently movablefree ends. The core portion and/or the shell portion may include aradioactive material.

BRIEF DESCRIPTION OF THE DRAWINGS

For a further understanding of the objects and advantages of the presentinvention, reference should be made to the following detaileddescription, taken in conjunction with the accompanying figures, inwhich:

FIG. 1 shows an exemplary large intact specimen percutaneous biopsydevice in operation.

FIG. 2 shows further aspects of the exemplary large intact specimenpercutaneous biopsy device of FIG. 1 in operation.

FIG. 3 shows further aspects of the exemplary large intact specimenpercutaneous biopsy device of FIG. 1 in operation.

FIG. 4 shows still further aspects of the exemplary large intactspecimen percutaneous biopsy device of FIG. 1 in operation.

FIG. 5 shows further aspects of the exemplary large intact specimenpercutaneous biopsy device of FIG. 1 in operation.

FIG. 6A shows further aspects of the exemplary large intact specimenpercutaneous biopsy device of FIG. 1 in operation, and illustrates thecreation of a cavity within the soft tissue from which the excisedspecimen was taken.

FIG. 6B is a cross sectional view of the post treatment cavity of FIG.6A, taken along cross-sectional line II′.

FIG. 7 shows further aspects of the exemplary large intact specimenpercutaneous biopsy device of FIG. 1 in operation, and furtherillustrates the creation of a cavity within the soft tissue from whichthe specimen was taken, with the aforementioned narrow neck or accesspath connecting the cavity to the skin.

FIG. 8 shows an exemplary delivery device for a post-biopsy cavitytreatment implant, according to an embodiment of the present invention.

FIG. 9 shows the delivery device of FIG. 8 in operation, delivering apost-biopsy cavity treatment implant according to an embodiment of thepresent invention within the cavity of FIG. 7.

FIG. 10A shows the cavity of FIG. 7, after the implantation of thepost-biopsy cavity treatment implant shown in FIGS. 8 and 9, with thepercutaneous incision closed.

FIG. 10B shows the cavity of FIG. 7, after the implantation of thepost-biopsy cavity treatment implant shown in FIGS. 8 and 9 in anotherorientation, with the percutaneous incision closed.

FIG. 10C shows the cavity of FIG. 7, after the implantation of apost-biopsy cavity treatment implant according to another embodiment ofthe present invention, with the percutaneous incision closed.

FIG. 11 shows a post-biopsy cavity treatment implant having apredetermined pore architecture, according to an embodiment of thepresent invention.

FIG. 12 shows another post-biopsy cavity treatment implant havinganother predetermined pore architecture, according to another embodimentof the present invention.

FIG. 13A shows a post-biopsy cavity treatment implant that includes aplurality of fibers, according to another embodiment of the presentinvention.

FIG. 13B shows a cross-section of a post-biopsy cavity treatmentimplant, according to another embodiment of the present invention.

FIG. 13C shows a portion of another post-biopsy cavity treatmentimplant, according to a further embodiment of the present invention.

FIG. 13D shows another post-biopsy cavity treatment implant, accordingto still another embodiment of the present invention.

FIG. 13E shows another post-biopsy cavity treatment implant, accordingto still another embodiment of the present invention.

FIG. 14A shows a post-biopsy cavity treatment implant that includes aplurality of fibers having predetermined pore architectures, accordingto another embodiment of the present invention.

FIG. 14B shows a front view of a post-biopsy cavity treatment implant,according to another embodiment of the present invention.

FIG. 14C shows a portion of another post-biopsy cavity treatmentimplant, according to a further embodiment of the present invention.

FIG. 14D illustrates the stacked structure of a post-biopsy cavitytreatment implant, according to a further embodiment of the presentinvention.

FIG. 14E illustrates the stacked structure of another post-biopsy cavitytreatment implant, according to a further embodiment of the presentinvention.

FIG. 14F illustrates the stacked structure of a post-biopsy cavitytreatment implant, according to a further embodiment of the presentinvention.

FIG. 14G illustrates the stacked structure of another post-biopsy cavitytreatment implant, according to a further embodiment of the presentinvention.

FIG. 15A shows a post-biopsy cavity treatment implant that includes aradiopaque and/or echogenic member around which one or more fibers arewound, according to another embodiment of the present invention.

FIG. 15B shows a post-biopsy cavity treatment implant that includes acore portion surrounded by an outer shell portion, each of the core andshell portions having a predetermine core architecture, according toanother embodiment of the present invention.

FIG. 15C is a cross-sectional representation of the implant of FIG. 15B,taken along cross-sectional line II-II′.

FIG. 15D shows a post-biopsy cavity treatment implant that includes acore portion having a first predetermine core architecture surrounded byan outer shell portion formed by a plurality of wound collagenous fibershaving a second predetermined pore architecture, according to anotherembodiment of the present invention.

FIG. 15E shows a post-biopsy cavity treatment implant that includes acore portion having a first predetermine core architecture surrounded byan outer shell portion formed by a plurality of collagenous fibershaving a second predetermined pore architecture, according to anotherembodiment of the present invention.

FIG. 15F is a cross-sectional view of the embodiment of FIG. 15D, takenalong cross-sectional line I-I′.

FIG. 16 is a photomicrograph of a collagen matrix having a predeterminedpore architecture with post-biopsy cavity treatment implants accordingto embodiments of the present invention may be constructed.

FIG. 16 is a photomicrograph of a collagen matrix having a predeterminedpore architecture with post-biopsy cavity treatment implants accordingto embodiments of the present invention may be constructed.

FIG. 17 is a photomicrograph of a collagen matrix having anotherpredetermined pore architecture with post-biopsy cavity treatmentimplants according to embodiments of the present invention may beconstructed.

FIG. 18 is a photomicrograph of a collagen matrix having still anotherpredetermined pore architecture with post-biopsy cavity treatmentimplants according to embodiments of the present invention may beconstructed.

FIG. 19 is a photomicrograph of a collagen matrix having a still furtherpredetermined pore architecture with post-biopsy cavity treatmentimplants according to embodiments of the present invention may beconstructed.

FIG. 20 is a photomicrograph of a collagen matrix having yet anotherpredetermined pore architecture with post-biopsy cavity treatmentimplants according to embodiments of the present invention may beconstructed.

FIG. 21 combination of photomicrographs of collagen matricesillustrating the formation of a stacked laminate structure including afirst layer having a first predetermined pore architecture and a secondlayer having a second predetermined pore structure, according to anembodiment of the present invention.

FIG. 22 is a combination of photomicrographs of collagen matrices thatcollectively illustrate a post-biopsy cavity treatment implant having apredetermined pore density gradient and/or predetermined graduatedcrosslinking gradient, according to a further embodiment of the presentinvention.

FIG. 23 is a combination of photomicrographs of collagen matrices thatcollectively illustrate a post-biopsy cavity treatment implant accordingto another embodiment of the present invention.

FIG. 24 shows a post-biopsy cavity treatment implant that includes acore portion surrounded by an outer shell portion, the core portionincluding a radiopaque element and the core and shell portions havingmutually different and predetermined pore architectures, according toanother embodiment of the present invention.

FIG. 25 shows the post-biopsy cavity treatment implant of FIG. 24 loadedinto an exemplary delivery device, according to an embodiment of thepresent invention.

FIG. 26 shows a post-biopsy cavity treatment implant according to astill further embodiment of the present invention, in various stages ofmanufacture.

FIG. 27 shows the post-biopsy cavity treatment implant of FIG. 26 loadedinto an exemplary delivery device, according to an embodiment of thepresent invention.

FIG. 28 shows the post-biopsy cavity treatment implant of FIGS. 26 and27 during implantation, according to an embodiment of the presentinvention.

FIG. 29 shows the post-biopsy cavity treatment implant of FIG. 28 afterimplantation, illustrating the manner in which the implant may expandand/or unfold within the cavity after implantation, according to anembodiment of the present invention.

FIG. 30 shows a post-biopsy cavity treatment implant according toanother embodiment of the present invention, in various stages ofmanufacture.

FIG. 31 shows the post-biopsy cavity treatment implant of FIG. 30 loadedinto an exemplary delivery device, according to an embodiment of thepresent invention.

FIG. 32 shows a post-biopsy cavity treatment implant according to yetanother embodiment of the present invention, in a configuration prior tofolding and/or compression.

FIG. 33 shows the post-biopsy cavity treatment implant of FIG. 32 in oneof many possible folded configurations, according to still anotherembodiment of the present invention.

FIG. 34 shows a core portion suitable for use in conjunction with thepresent post-biopsy cavity treatment implant, according to anotherembodiment of the present invention.

FIG. 35 shows a post-biopsy cavity treatment implant incorporating thecore portion of FIG. 34, according to yet another embodiment of thepresent invention, in a configuration prior to folding and/orcompression.

FIG. 36 shows further core portions suitable for use in conjunction withthe present post-biopsy cavity treatment implant, according to anotherembodiment of the present invention.

FIG. 37 shows a post-biopsy cavity treatment implant incorporating thecore portions of FIG. 36, according to a further embodiment of thepresent invention, in a configuration prior to folding and/orcompression.

FIG. 38 shows another core portion suitable for use in conjunction withthe present post-biopsy cavity treatment implant, according to anotherembodiment of the present invention.

FIG. 39 shows an exemplary radiopaque element suitable for use inconjunction with the present post-biopsy cavity treatment implant,according to a still further embodiment of the present invention.

FIG. 40 shows another radiopaque element suitable for use in conjunctionwith the present post-biopsy cavity treatment implant, according to yetanother embodiment of the present invention.

FIG. 41 shows a post-biopsy cavity treatment implant, according to afurther embodiment of the present invention, in a configuration prior tofolding and/or compression.

FIG. 42 shows a post-biopsy cavity treatment implant, according toanother embodiment of the present invention, in a configuration prior tofolding and/or compression.

DESCRIPTION OF THE EMBODIMENTS OF THE INVENTION

FIGS. 1-7 show aspects of a percutaneous method for cutting, collectingand isolating a tissue specimen and the subsequent creation of a cavitywithin which embodiments of the present inventions may be implanted. Theexcisional device shown in FIGS. 1-7 is described in commonly assignedU.S. Pat. No. 6,022,362 and in copending and commonly assigned patentapplication Ser. No. 10/189,277 filed on Jul. 3, 2002, the disclosure ofeach being incorporated herein in its entirety. Although embodiments ofthe present invention are described relative to a cavity created by theexcisional device shown in FIGS. 1-7, it is to be understood that thepresent inventions are not to be limited thereby. Indeed, embodiments ofthe present invention may be advantageously utilized to treat cavitiesof various shapes and sizes created by other devices, including devicesthat obtain tissue specimen through coring or ablation techniques, forexample.

As shown in FIG. 1, the excisional device 100 is introduced into a massof tissue 110 through the skin 102, with the integrated cut and collectassembly 112 thereof in a retracted position. The device 100 is thenadvanced such that the assembly 112 is adjacent to the target lesion108. The assembly 112 may then be energized and expanded as shown inFIG. 2 by acting upon the actuator 118. As the assembly 112 is RFenergized and expanded, it cuts the tissue through which it travels. Asshown at FIG. 3, the excisional device 100 may then be rotated, whilethe assembly 112 remains energized, causing the leading edge thereof tocut through the tissue, preferably with clean margins. The expandedintegrated cut and collect assembly 112 deploys the membrane 114 and thecut specimen 108 is collected in the open bag formed by the close-endeddeployed flexible membrane 114. As shown in FIGS. 4 and 5, the rotationof the device 100 may then be continued as needed, preferably underultrasonic guidance. To fully sever the specimen 108 from thesurrounding tissue 110, the assembly 112, while still energized, isretracted to capture, encapsulate and isolate the specimen 108 withinthe flexible membrane 114. As shown in FIG. 6A, the specimen 108 maythen be recovered by retracting the device 100 through the retractionpath 127, stretching it as necessary. FIG. 7 shows a fully retracteddevice 100, containing a collected and isolated specimen 108.

As shown in FIGS. 6A-7, after the procedure described above or after anyprocedure in which a substantial volume of tissue specimen is taken, avoid or cavity 126 is created where the tissue specimen 108 used to be.Cavities as shown at 126 may require different post proceduraltreatments, as compared to procedures such as needle biopsies due to thedifferent nature, size and shape created by the biopsy device. As shownin FIGS. 6A and 6B, the exemplary cavity 126 is characterized by arelatively narrow access path 127 that emerges into a larger cavitychamber 128 formed by the extension and rotation of the cut and collectassembly 112 during the above-described procedure. After the device 100is withdrawn from the patient as shown in FIG. 7, portions of the cavity126 and/or access path 127 may settle and collapse somewhat, as theinterior tissue walls defining the cavity 126 are no longer supported bythe tissue previously occupying that space.

Treating the post-biopsy cavity 126 is desirable for a variety ofreasons. One such reason is to accommodate the unique size and shape ofthe cavity 126 created by the device 100. It is desirable to influenceand/or promote the healing process of the cavity, and to do so in apredictable manner. One aspect of influencing the healing process of thecavity 126 is promoting the growth of new connective tissue within thecavity 126 in a predictable manner. Indeed, it is desirable to influenceand promote both tissue ingrowth within the cavity and to influence theformation of hematomas and seromas. Another reason for treating thepost-biopsy cavity 126 is to modify it in such a manner as to render itrecognizable immediately and preferably long after the procedure thatcreated the cavity 126. The cavity 126, left untreated, may be visibleunder ultrasound. However, that may not be the case and it is believedto be desirable to at least partially fill the cavity 126 with a cavitytreatment implant that will render the cavity 126 clearly visible undervarious imaging modalities, including modalities such as ultrasound,X-ray, MRI, elastography, microwave and the unaided eye, for example.Such visibility may be due to the structure of a cavity treatmentimplant or devices implanted within the cavity and/or a recognizablepattern of tissue ingrowth caused or influenced by the continuing orpast presence of post-biopsy cavity treatment implants disclosed herein.Other desirable attributes of embodiments of the implantable post-biopsycavity treatment implant of the present invention include hemostasis,and the ability to deliver one or more therapeutic agents to the patientat the post-biopsy cavity treatment implant site such as, for example,lido/epi, Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), tissue growthfactors, anti-neoplastic medications (to name a few) or combinations ofthe above and/or others. Filling the cavity 126 may have other benefits,including cosmetic. Indeed, filling the cavity and promoting a smooth,gradual, recognizable and orderly tissue ingrowth pattern may preventdimpling, skin depressions and the like sometimes associated with theremoval of a large intact specimen during the biopsy procedure.Embodiments of the present invention may also find utility inaugmentation or reconstructive procedures for the breast or other softtissue.

According to an embodiment of the present invention, the post-biopsycavity treatment implant may have a size and a shape that at leastpartially fills the cavity. Advantageously, the present post-biopsycavity treatment implant, after insertion, may have a characteristicshape that is readily perceptible and recognizable through variousmodalities, including, for example, ultrasound, X-ray or MRI. The shapeof the present post-biopsy cavity treatment implant may also influencethe manner in which tissue growths therein. Preferably, embodiments ofthe present post-biopsy cavity treatment implant should be shaped anddimensioned so as to uniquely accommodate the size and shape of thecavity 126 created by the device 100 of FIGS. 1-7. However, embodimentsof the present invention may be readily sized and shaped to specificallyaccommodate cavities of any shape and size created by other devicesand/or biopsy or therapeutic surgical procedures.

According to an embodiment thereof, the present invention may include animplantable post-biopsy cavity treatment implant having one or more ofthe structures, characteristic and properties described herein. As shownin FIG. 8, the implantable post-biopsy cavity treatment implant 802, ina pre-implanted state, may be loaded into an introducer, an illustrativeexample of which is shown at reference numeral 804. The introducer 804may then be inserted into the tissue 110 through the access path 127 andat least partially into the cavity chamber 128 of the cavity 126. Thepost-biopsy cavity treatment implant 802 may then be delivered to thecavity 126 and thereafter be left in place and the introducer 804withdrawn. The pre-implanted state of the post-biopsy cavity treatmentimplant 802 is preferably a state in which the post-biopsy cavitytreatment implant occupies its minimum volume. According to anembodiment of the present invention, the pre-implanted state of thepost-biopsy cavity treatment implant 802 is an at least partiallylyophilized (e.g., at least partially dehydrated) state and thepost-biopsy cavity treatment implant may be configured to swell whenplaced within a biological fluid environment such as the cavity 126. Thepost-biopsy cavity treatment implant 802 may define a proximal portion806 that is closest to the access path 127 and a distal portion 808 thatis relatively further away from the access path 127 than is the proximalportion 806.

Whereas FIG. 9 shows the present post-biopsy cavity treatment implant802 immediately after implantation in tissue (i.e., still in a state inwhich it occupies its minimum volume), FIG. 10A shows the state of thepresent post-biopsy cavity treatment implant 802 a short period of timeafter implantation. As shown, the post-biopsy cavity treatment implant802 is no longer in its pre-implanted state. Indeed, the post-biopsycavity treatment implant 802, having been placed in a biological fluidenvironment (such as the patient's tissue), begins to swell. Accordingto an embodiment of the present invention, the post-cavity treatmentimplant 802 may be configured to swell in a uniform manner. In anotherexample, the surgeon may inject fluids after placing the device with theintent to “wet” the present post-cavity treatment implant. Substancessuch as saline, fibrin solution or other catalyst or activator may beused for that purpose. The activator or swelling fluid could be injectedpreferentially at the proximal portion 806 or selectively at points inthe post-cavity treatment implant to cause it to secure itself inposition inside the cavity 126. Alternatively, as part of the insertiondevice (such as, for example, the introducer 804), an integral vial maybe crushed by the surgeon to release the activating fluid (for example,an aqueous solution, dye/pigment) in the area of the proximal portion806 for example, thus causing rapid swelling of that region.Alternately, the introducer 804 may define an internal lumen 811 overits length and may include a fluid injection port 812 at the proximalend of the device. Fluids such as the aforementioned saline or fibrinmay then be introduced into the cavity 126 through the fluid injectionport 812 and the internal lumen 811 to cause the rapid swelling of theimplant or for any other reason. Delivering such fluids can beespecially useful if the field within the cavity is relatively dry ascan occur in the ideal case. According to another embodiment of thepresent invention, the post-biopsy cavity treatment implant 802 may beconfigured to swell non-uniformly. Such non-uniform swelling rates maybe advantageous in insuring that the post-biopsy cavity treatmentimplant 802 stays where it is placed during the implantation procedure.In the embodiment shown in FIG. 10A, the post-biopsy cavity treatmentimplant 802 is structured such that the rate at which the proximalportion 806 swells faster than the rate at which the distal portion 808swells. When implanted in a cavity 126 such as shown in FIGS. 6A, 6B, 7,9 and 10, the proximal portion 806 swells faster than the distal portion808, thereby serving to maintain the post-biopsy cavity treatmentimplant 802 within the cavity chamber 128 of the cavity 126. This may beachieved by, for example, controlling the crosslinking densities orcreating a gradient of crosslinking densities within the post-biopsycavity treatment implant 802, where certain regions of the post-biopsycavity treatment implant 802 are controlled to have a greatercrosslinking density than other regions, resulting in a non-uniformswelling pattern over the extent of the device 802. For example, thedistal portion 808 may be configured to be relatively more crosslinkedthan the proximal portion 806 thereof, resulting in the proximal portion806 swelling more and/or faster than the distal portion 808. As theproximal portion 806 of the post-biopsy cavity treatment implant 802swells, it preferably swells from a shape in which it is easilyimplantable through the access path 127 to a shape and size wherein atleast the proximal portion 806 thereof no longer fits through the accesspath 127. As this swelling occurs rapidly after the post-biopsy cavitytreatment implant 802 comes into contact with the fluids present withinthe cavity 126, the surgeon may retract the introducer 804 from thecavity 126, close the initial incision and be confident that thepost-biopsy cavity treatment implant 802 has remain in its intendedposition, squarely within the cavity chamber 128 of the cavity 126, andhas not migrated back into the access path 127.

The post-biopsy cavity treatment implant 802 may alternatively bestructured such that its distal 808 portion swells faster than itsproximal portion 806 such as shown in FIG. 10B, such that both theproximal and distal portions of the post-biopsy cavity treatment implantswell relatively faster than the portion thereof between the proximaland distal portions or such that the proximal and distal portions 852,856 of the implant 850 swell relatively slower than a middle portion854, as shown in FIG. 10C. Alternatively still, the post-biopsy cavitytreatment implant 802 may not have well defined proximal and distalportions and the post-biopsy cavity treatment implant 802 may bestructured such that one portion thereof swells at a different rate thananother portion thereof, for the purpose outlined above or for differentpurposes altogether—such as cavity shaping, for example. As suggested inFIGS. 9 and 10A, 10B, the post-biopsy cavity treatment implant 802 maybe formed from a tightly rolled up sheet of swellable material.Alternatively, the post-biopsy cavity treatment implant 802 may beformed of stacked layers of swellable material as shown in FIG. 10C.Alternatively still, the post-biopsy cavity treatment implant 802 may beformed as a single unitary and homogeneous mass of swellable materialand molded or cut (stamped) into the desired shape. Other embodimentsinclude post-biopsy cavity treatment implants formed of or includingfibers, fibrils and/or bundles of fibers and/or fibrils.

According to embodiments of the present invention, the presentpost-biopsy cavity treatment implant may include or be formed ofbiocompatible and water swellable material, such as collagen, forexample. The collagen molecule is rod-shaped triple helix and consistsof a three polypeptide chains coiled about each other. Besides thecentral triple helical region of the collagen molecule, there areterminal peptides regions known as telopeptides. These telopeptides arenon-helical and are subdivided into two groups; namely, amino terminalsand carboxyl terminals. Intermolecular crosslinking between triplehelical molecules of collagen occurs in the telopeptides regions.Crosslinking may also occur within the central triple helical region ofthe collagen molecule, and is known as intramolecular crosslinking. Itis the control of the formation and density of such crosslinks that isresponsible for some of the mechanical, physicochemical and biologicalproperties of the embodiments of the present post-biopsy cavitytreatment implant disclosed herein.

The embodiments of the present post-biopsy cavity treatment implant maybe selectively biodegradable and/or bio-absorbable such that it degradesand/or is absorbed after its predetermined useful lifetime is over. Aneffective way of controlling rate of biodegradation of embodiments ofthe present post-biopsy cavity treatment implant is to control andselectively vary the number and nature (e.g., intermolecular and/orintramolecular) of crosslinks in the implant material. Control of thenumber and nature of such collagen crosslinks may be achieved bychemical and/or physical means. Chemical means include the use of suchbifunctional reagents such as aldehyde or cyanamide, for example.Physical means include the application of energy through dehydrothermalprocessing, exposure to UV light and/or limited radiation, for example.Also, a combination of both the chemical and the physical means ofcontrolling and manipulating crosslinks may be carried out. Aldehydessuch as glutaraldehydes, for example, are effective reagents ofcollagenous biomaterials. The control and manipulation of crosslinkswithin the collagenous matrix of the present post-surgery cavitytreatment implant may also be achieved, for example, through acombination of dehydrothermal crosslinking and exposure to cyanamide.For example, the present post-surgery cavity treatment implant may,through proper control of the crosslinking density within the collagenmatrix thereof, be designed and implemented to remain long term in situat the implant site within the cavity 126. Crosslinking density may beindirectly measured, for example, via measurement of the swelling ratiowhere identical dry and wetted samples are weighted and weight iscompared.

According to further embodiments of the present invention, thepost-biopsy cavity treatment implant may be formed of or include otherbiomaterials such as, for example, bioresorbable poly(ester)s such aspolylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolides)(PLGA), polyglyconate, polyanhydrides and their co-polymers, PEG,cellulose, gelatins, lipids, polysaccharides, starches and/orpolyorthoesters and the like. According to an embodiment of the presentinvention, the present post-biopsy cavity treatment implant may beformed of or include collagen having a predetermined structure. Suchpredetermined structure refers not only to the overall shape of theimplant, but also to the structure of its internal collagen matrix.Indeed, embodiments of the present invention include a macroporouscross-linked polymer matrix having a predetermined pore architecture. A“pore”, as the term is used herein, includes a localized volume of thepresent post-biopsy cavity treatment implant that is free of thematerial from which the post-biopsy cavity treatment implant is formed.Pores may define a closed and bounded volume free of the material fromwhich the post-biopsy cavity treatment implant is formed. Alternatively,pores may not be bounded and many pores may communicate with one anotherthroughout the internal matrix of the present post-biopsy cavitytreatment implant. The pore architecture, therefore, may include closedand bounded voids as well as unbounded and interconnecting pores andchannels. The internal structure of the post-biopsy cavity treatmentimplant according to embodiment of the present invention defines poreswhose dimensions, shape, orientation and density (and ranges anddistributions thereof), among other possible characteristics aretailored so as to maximize the visibility of the resultant post-biopsycavity treatment implant 802 under various modalities, notablyultrasound and X-ray, for example. Unlike polymeric matrices thatcontain bubbles of gas through a process in which gas is forced througha dispersion in a hydrated state, embodiments of the present post-biopsycavity treatment implant have an internal structure that definesinternal voids without requiring such gas to be forced therethrough.There are numerous methods and technologies available for the formationcollagenous matrices of different pore architectures and porosities. Bytailoring the dimensions, shape, orientation and density of the pores ofthe present implant, a recognizable pattern of post-biopsy cavitytreatment implant material may be formed that may be readily visualizedunder, for example, ultrasound, X-ray, elastography or microwaveradiation. This recognizable pattern may then influence the pattern oftissue ingrowth within the cavity 126, forming a porous scaffold on andwithin which tissue may infiltrate and grow. In turn, this pattern oftissue ingrowth may be readily recognizable under ultrasound and/orother imaging modalities discussed above long after the post-biopsycavity treatment implant has been absorbed by the body or has degraded.

According to an embodiment of the present invention, the post-biopsycavity treatment implant may be formed of or include a collagen matrixhaving a predetermined pore architecture. For example, the post-biopsycavity treatment implant may include one or more sponges of lyophilizedcollagen having a predetermined pore architecture. Suitable collagenmaterial for the post-biopsy cavity treatment implant may be availablefrom, for example, DEVRO, Integra Life Sciences, Collagen Matrix andKensey Nash, among others. The present post-biopsy cavity treatmentimplant, after implantation in the cavity 126, swells on contact withvarious body fluids therein and substantially fills a predeterminedportion or the entire biopsied cavity, and does so in predictablemanner.

Such a post-biopsy cavity treatment implant may be configured to have ahemostatic functionality to stop bleeding within the cavity 126 througha biochemical interaction with blood (such as coagulation) and/or otherbodily fluids. The post-biopsy cavity treatment implant may, accordingto further embodiments, also be used to medically treat the patient.That is, the porous matrix of the present post-biopsy cavity treatmentimplant may be imbibed or loaded with a therapeutic agent to deliver theagent through elution at the cavity 126. Such a therapeutic agent mayinclude, for example, an antibiotic agent, an analgesic agent, achemotherapy agent, an anti-angiogenesis agent or a steroidal agent, toname but a few of the possibilities.

The post-biopsy cavity treatment implant 802 shown in FIGS. 9 and 10 maybe formed of one or more thin sheets of collagen material having apredetermined (and controlled) pore architecture that has been rolled upinto a cylinder shape. As the post-biopsy cavity treatment implant 802swells with water from the cavity 126, it may unroll partially orentirely, and at least partially fill the cavity 126, including at leasta portion of the cavity chamber 128. Some of the access path 127 mayalso be filled as the post-biopsy cavity treatment implant 802 swells.The post-biopsy cavity treatment implant 802, according to embodimentsof the present invention, has a predetermined pore architecture or acombination of predetermined pore architectures, as will be describedhereunder with reference to the drawings. The description of the figuresbelow assumes that the post-biopsy cavity treatment implant is formed ofor contains collagen, it being understood that the embodiments of thepresent invention disclosed herein are not limited to collagen and thataspects of the present inventions may readily be applied to suchnon-collagen containing post-biopsy cavity treatment implants.

FIG. 11 shows a post-biopsy cavity treatment implant 1100 havingpredetermined pore architectures, according to an embodiment of thepresent invention. As shown therein, the post-biopsy cavity treatmentimplant 1100 may include a first portion 1102 and a second portion 1104.The collagen matrix of the first portion 1102 of the device 1100 definesa plurality of pores 1106 having a first predetermined pore architectureand the collagen matrix of the second portion 1104 of the device 1100defines a plurality of pores 1108 having a second predetermined porearchitecture. The dimensions of the layers or portions may be selectedat will, preferably accounting for the dimensions of the cavity intowhich the device is to be inserted. As shown, the first porearchitecture features pores 1106 that are relatively small, have anarrow pore size distribution and are substantially randomly oriented.In contrast, the second pore architecture features pores 1108 that havea relatively larger size, have a wider pore size distribution, arepredominantly oriented along the axis indicated by double-headed arrow1110 and are less densely distributed than the pores 1106 of the firstportion 1102 of the post-biopsy cavity treatment implant 1100. Betweenthe first and second portions 1102 and 1104 lies the interface 1103. Asshown, the post-biopsy cavity treatment implant 1100 may be formed of afirst collagen matrix having a first predetermined pore architecture anda second collagen matrix having a second pore architecture. The twocollagen matrices may each be formed from separate collagen dispersions,each of which may be caused to form pores having predeterminedcharacteristics and may each be at least partially lyophilized andformed (e.g., molded, cut or stamped) into the desired shape (in theillustrative case of FIG. 11, a substantially cylindrical shape). Thetwo collagen plugs formed thereby may then be stacked one on the other,re-wetted and again lyophilized through a lyophilization process in aspecifically shaped mold (for example) to form the stacked laminatestructure shown in FIG. 11. Other methods of making the post-biopsycavity treatment implant 1100 may occur to those of skill in this art.Not only may the predetermined pore architectures of the first portion1102 and of the second portion 1104 cause these portions to be visibleunder, for example, ultrasound, but the interface 1103 therebetween mayalso be visualizable and recognizable under, for example, ultrasound asthe boundary between two regions having a pronounced densitydifferential. As can be seen, the post-biopsy cavity treatment implant1100 is not formed of a rolled up sheet of material, as is thepost-biopsy cavity treatment implant 802 in FIGS. 9 and 10. Instead, thepost-biopsy cavity treatment implant 1100 is formed of solid matrices ofcollagenous material. It is to be understood that the pore architectureof the first and second portions 1102, 1104 may be varied at will by,for example, changing the porosity and/or crosslinking of the collagenchains, the pore density, the distribution of pore size, the orientationof the pores and the shape of the pores, to mention a few of thepossible pore parameters. By judiciously choosing the pore architecturesof the first and second portions 1102, 1104, one end of the post-biopsycavity treatment implant 1100 may be caused to swell at a faster ratethan the other end thereof. This is the case illustrated in FIG. 10.

Moreover, the cross-sectional characteristics of the post-biopsy cavitytreatment implant 1100 may be changed. For example, the first portion1102 may form a cylindrical inner core of collagenous material having afirst predetermined pore architecture and the second portion 1104 mayform a cylindrical outer shell around the inner core and may define asecond pore architecture. In this manner, the outer surface of thepost-biopsy cavity treatment implant 1100 may swell at a different rate(e.g., faster) than the rate at which the inner core swells. Moreover,the pore architectures may be chosen to maximize not only waterabsorption, but also to promote tissue ingrowth, to facilitate imagingand/or may be tailored to contain and release a pharmaceutical agent ata controllable rate and/or under predetermined conditions.Alternatively, the inner core may be formed of or include anon-collagenous material (such as a polylactic or polyglycolic material,for example) and the outer shell may include a collagenous material, forexample. The outer shell may include a solid matrix of collagenousmaterial having a predetermined pore architecture and/or may includewound fibers of collagenous material having a predetermined porearchitecture, for example.

FIG. 12 shows a post-biopsy cavity treatment implant 1200 havingpredetermined pore architectures, according to another embodiment of thepresent invention. As shown, the post-biopsy cavity treatment implant1200 includes a first portion 1202 and a second portion 1204, each ofwhich has a predetermined pore architecture. It is to be noted that thepresent post-biopsy cavity treatment implants may have more than the twoportions shown in both FIGS. 11 and 12 (or may define only a singleportion). As shown, the post-biopsy cavity treatment implant 1200 isshaped as a substantially rectangular sponge. The first portion 1202 isstacked on the second portion 1204. As with the embodiment shown in FIG.11, the first and second portions may have pore architectures thatfacilitates tissue ingrowth, wound healing and are readily visualizableand/or recognizable under one or more imaging modalities. The differentpore architectures of post-biopsy cavity treatment implants according toembodiments of the present invention may also be chosen so as tomaximize the visibility of the interface (such as reference numeral 1203in FIG. 12) therebetween under the desired imaging modality such as, forexample, ultrasound.

Post-biopsy cavity treatment implants according to embodiments of thepresent invention need not be formed as a solid mass of collagen (FIGS.11, 12) or as a rolled up sheet of collagen (FIGS. 9, 10). FIGS. 13A,13B and 13C show various other configurations for the present implant.As shown therein, embodiments of the present invention may include or beformed of a bundle of fibers or fibrils 1302 of (for example)collagenous material having one or more predetermined porearchitectures. The pores defined within the collagen matrix of all orsome of the fibers are not shown in FIGS. 13A-13C, but are neverthelesspresent. The bundle 1300 of fibers shown in FIG. 13A may be used to formpost-biopsy cavity treatment implants by, for example, forming them intoa rope-like structure as shown in FIG. 13B. In the cross-sectionalrepresentation of FIG. 13B, the longitudinal axis of the individualconstituent fibers is perpendicular to the plane of the page on whichthey are printed. Post-biopsy cavity treatment implants may also beformed from the bundle 1300 of FIG. 13A by cutting (at 1304, forexample) the bundle 1300 into a plurality of sections at an angle thatis (for example) perpendicular to the longitudinal axis of the fibers1302, so as to form a post-biopsy cavity treatment implant whoseconstituent fibers run from one end of the post-biopsy cavity treatmentimplant to the other end thereof, as shown in the detail representationof FIG. 13C. According to an embodiment of the present invention, apost-biopsy cavity treatment implant may be formed of a volume ofcollagenous material having a predetermined pore architecture or acombination of several bounded volumes of collagenous materials, eachwith a predetermined pore architecture. For example, several spongeshaving the structure shown in FIG. 13C may be stacked onto each other todefine a laminate structure having a layered, composite porearchitecture.

FIG. 13D shows another embodiment of the present post-biopsy cavitytreatment implant. As shown, the implant 1306 includes a first portion1308 and a second portion 1310. According to an embodiment of thepresent invention, the first portion 1308 may include a solid matrix ofcollagenous material 1312 having a first predetermined porearchitecture. The second portion 1310 may include a plurality of fibersor fibrils 1314. The plurality of fibers may also be formed of orinclude collagenous material, and this collagenous material may have thesame pore architecture as the first portion 1308 or a different porearchitecture. The plurality of fibers may be formed or includenon-collagenous material, such as polylactic or polyglycolic acid, forexample. In the case wherein the plurality of fibers 1314 are formed ofa collagenous material, after implantation in a biological fluidenvironment such as a cavity within a patient, the second portion 1310may swell at a faster rate than the first portion 1310, as theconstituent fibers 1314 thereof may be exposed to the biological fluidenvironment of the cavity over their entire surface. This swelling ratedifferential between the first and second portions 1308, 1310 may serveto further secure the implant 1306 within the cavity. In the casewherein the cavity is relatively dry, the physician may choose tointroduce a volume of an aqueous solution, such as saline, into thecavity to speed the swelling of the implant 1306. The implant 1306 maybe formed from a collagen dispersion in a mold configured to form thefirst portion 1308 and the second portion 1310 and lyophilized.Alternatively, the fibers 1314 may be formed after lyophilization bycutting the implant 1306 so as to form the plurality of fibers 1314.Alternatively still, the first and second portions 1308, 1310 may beformed by superimposition of the first and second portions 1310, 1310,as discussed above. Other means of forming the first and second portions1310, 1312 may occur to those of skill in this art.

FIG. 13E shows another embodiment of the present post-biopsy cavitytreatment implant. As shown therein, the implant 1316 is similar to theembodiment of FIG. 13D, but for the addition of a third portion 1318 onanother surface of the first portion 1308. The third portion 1318 may beformed as detailed above relative to second portion 1310. The porearchitecture of the third portion 1318 may be the same as that of thefirst portion 1308 and the second portion 1310, or may be differenttherefrom. It should be noted that various modifications to theembodiments of FIGS. 13D and 13E may be envisaged. For example, theembodiment of the implant 1316 of FIG. 13E may be modified to includeadditional fibers or fibrils projecting from other surfaces of the firstportion 1308. Other modifications may occur to those of skill in thisart, and all such modifications are deemed to fall within the scope ofthe present invention.

FIG. 14A through 14E show other illustrative embodiments of thepost-biopsy cavity treatment implants according to the presentinvention. As shown in FIG. 14A, two or more bundles of fibers ofcollagenous material (for example—the fibers may be made of or includeother materials) may be used in the formation of post-biopsy cavitytreatment implants according to embodiments of the present invention. Asshown, the pores within the fibers of the first bundle 1402 maycollectively define a first pore architecture, whereas the pores withinthe fibers of a second bundle 1404 may collectively define a second porearchitecture that is different from the first pore architecture. The twobundles 1402, 1404 may then be joined together, for example, byre-wetting the bundles, stacking them and lyophilizing the compositestructure. The length and diameter of the fibers may be selected andvaried at will. The fibers or bundles thereof may even be woventogether. From this composite structure, post-biopsy cavity treatmentimplants may be formed. As shown in FIG. 14B, the bundles of fibers maybe arranged in a cylindrical shape, for example. Such a cylindricalshape may include an inner core 1406 of fibers having a first porearchitecture and an outer shell 1408 surrounding the inner core 1406.The outer shell may include fibers having a second pore architecturethat is different from the pore architecture of the inner core 1406.FIG. 14C shows a detail of a post-biopsy cavity treatment implant havinga first portion 1402 of fibers having a first pore architecture and asecond portion 1404 having a second pore architecture, formed, forexample, by cutting the composite structure of FIG. 14A at 1410.Alternatively still, the fibers may be arranged such that theconstituent fibers thereof closer to the center of the post-biopsycavity treatment implant conform to a first pore architecture whereasthe outside constituent fibers thereof conform to a second porearchitecture that is different from the first pore architecture. Asshown in the exploded views of FIGS. 14D and 14E, the post-biopsy cavitytreatment implant may be have a layered laminate structure in whichsheets formed of fibers (or woven fibers) having a first porearchitecture are stacked onto sheets formed of fibers having a secondpore architecture. As shown in FIG. 14E, many variations on this themeare possible. As shown therein, the orientation of the fibers (and thusof the pores defined by the collagenous matrix thereof) may be varied.For instance, whereas the fibers of the first (top or outer, forexample) portion of the post-biopsy cavity treatment implant may beoriented in a first direction, whereas the fibers of the second (bottomor inner, for example) portion of the post-biopsy cavity treatmentimplant may be oriented along a direction that is different from thefirst direction (perpendicular thereto, for example). Imaging suchpost-biopsy cavity treatment implants within a cavity (such as shown at126 in FIGS. 9 and 10, for example) using sonography may yield an imagein which any fluids contained in the cavity 126 may appear substantiallyblack, because the sound waves travel directly through such anechoicmedia, and a gradation of visible structures defined by comparativelyhypoechoic layers or portions of the post-biopsy cavity treatmentimplant whose echogenicity is lower than the surrounding area anddefined by hyperechoic layers or portions of the post-biopsy cavitytreatment implant whose echogenicity is higher than the surroundingarea.

FIGS. 14F and 14G illustrate the stacked structure of a post-biopsycavity treatment implant, according to further embodiments of thepresent invention. The embodiments of FIGS. 14F and 14G are similar tothe embodiments shown in FIGS. 14D and 14E, but for the structure of thestacked sheets of collagenous material. In FIGS. 14F and 14G, thestacked sheets of collagenous material are not formed of fibers orfibrils, but instead are each formed of a solid mass of collagenousmaterial. The sheets may have the same or different pore architectures.Moreover, the sheets of collagenous material may define porearchitectures in which the predominant orientation of the pores isvaried. For example, some of the sheets may have a pore architecture inwhich the pores are predominantly oriented along the y-axis (FIG. 14F)or along the x-axis (FIG. 14G), for example. Alternatively, theconstituent sheets of collagenous materials may define porearchitectures in which other pore characteristics (size, shape, density,for example) are varied according to a predetermined pattern toinfluence tissue growth, visualization, etc. The resulting laminatestructure may be formed (e.g., molded or cut) in the desired shape ofthe implant. For example, the resulting laminate structure may then berolled into a cylindrical shape, as suggested in FIGS. 8 and 9, forexample.

FIG. 15A shows a post-biopsy cavity treatment implant according toanother embodiment of the present invention. As shown, the post-biopsycavity treatment implant 1500 includes an inner portion 1502 and anouter portion 1504. The inner portion 1502 may be radiopaque. Forexample, the inner portion 1502 may be or include a metallic element.The metallic element may have a simple bar shape as shown, or may have amore complex shape such as, for example, a ring. The inner portion 1502may have other structures to, for example, adhere or hook onto the wallsof the cavity 126. Wound around the inner portion 1502 is one or morefibers 1504 of swellable (collagenous, for example) material having oneor more predetermined pore architectures and/or one or more controlledcrosslinking densities. The inner portion may be completely encasedwithin the wound bundles of fibers or fibrils 1504 or may be onlypartially encased, as shown in FIG. 15A. The inner element 1502, ratherthan being radiopaque, may have a predetermined echogenicity so as to beimmediately recognizable under ultrasound. The inner element 1502,moreover, may include an inner reservoir configured to contain a volumeof therapeutic agent. For example, the inner element 1502 may bebioabsorbable and may be configured to release the containedpharmaceutical agent at a controlled rate. A plurality of fibers 1504(having the same or different pore architectures) may be wound about theinner element 1502, the windings thereof being oriented at a giveninclination or mutually different inclinations. Moreover, theembodiments of FIGS. 11 through 14E may advantageously be provided withan inner element as shown at 1502 and/or as described immediately above.

FIG. 15B and the cross-sectional representation of FIG. 15C show anotherembodiment of the present post-biopsy cavity treatment implant. As showntherein, the implant 1506 may include a first inner portion 1508 formingan inner core and a second outer portion 1510 forming an outer shellaround the first inner portion 1508. Both the first and second portionsmay be formed of or include a collagenous material. The first portion1508 may have a first predetermined pore architecture and the secondportion 1510 may have a second predetermined pore architecture that isdifferent from pore architecture of the first portion 1508. For example,the first portion 1508 may have a greater pore density (number of poresper unit volume) than the second portion 1510. In the exemplary implant1506 shown in FIGS. 15B and 15C, the pore architecture of the firstportion 1508 is such that the collagenous material thereof defines poresthat are both smaller and more densely packed than those defined by thecollagenous material of the second portion 1510. Although FIGS. 15B and15C show the implant 1506 as shaped as a right cylinder, the implant1506 may be molded into most any shape, to accommodate most any cavityshape. In this manner, the implant may be configured such that itsultimate size and shape after implantation and swelling, substantiallymatches the size and shape of the cavity in which it is implanted. Asshown in the cross-sectional representation of FIG. 15C, the firstportion 1508 of the implant 1506 may define an inner reservoir 1512(created as a void within the first portion 1508 or as a discretebiocompatible reservoir or pouch having a predetermined biodegradabilityrate). The inner reservoir 1512 may be pre-loaded with a dye/pigmentand/or a pharmaceutical agent, as indicated at 1514 in FIG. 15C. Thepharmaceutical agent may be configured to slowly release into the cavity126 as soon as the implant is inserted therein and/or may be configuredto require a physician or a RN to pinch or squeeze (or otherwise breach)the implant 1506 to rupture the reservoir 1512 to release thedye/pigment and/or pharmaceutical agent 1514 contained therein.

FIG. 15D shows another embodiment of the implant according to thepresent invention. The implant 1516 includes a first portion 1508defining a first pore architecture, such as described above relative toFIGS. 15B and 15C. The implant 1516 may include a reservoir 1512, andthe reservoir 1512 may contain a volume of dye/pigment and/or one ormore therapeutic agents. Wound around the first portion 1508 is one ormore fibers or fibrils of collagenous material defining a second porearchitecture that may be different from the first pore architecture. Thefibers or fibrils 1520 may completely encase the first portion 1508 ormay do so only partially, as shown in FIG. 15D. FIGS. 15E and 15F showanother embodiment of the present invention. In this embodiment, theimplant 1518 also includes a first portion 1508 defining a first porearchitecture, as described relative to FIGS. 15B-15D above. At leastpartially surrounding the first portion 1508 are a plurality of fibersor fibrils 1508 that define a second pore architecture that may bedifferent from the first pore architecture. Several layers of suchfibers or fibrils 1508 may be disposed around the first portion 1508, assuggested by the cross-sectional view of FIG. 15F.

Most any of the portions or layers of the embodiments disclosed hereinmay be configured to contain one or more dyes/pigments and/orpharmaceutical agents. The post-biopsy cavity treatment implantsdiscussed herein may be rendered selectively radiopaque by the selectivemechanical, chemical or physical incorporation of a radiopaque articlesor particles into the collagenous matrix of embodiments of the presentpost-biopsy cavity treatment implant. For example, the post-biopsycavity treatment implant may define pores having a predetermined andrecognizable architecture and may incorporate some radiopaque compoundor particles such as, for example barium sulfate or other commonly usedradiopaque or radioactive materials.

Embodiments of the present invention may also include recognizablearticles or substances within the collagenous matrix such as, forexample, dyes and/or pigments (i.e., including both synthetic dyes andnatural pigments). The dyes/pigments may be incorporated within thecollagenous dispersion that forms the constituent layers or portions ofthe embodiments of the post-biopsy cavity treatment implants disclosedherein. Such dyes/pigments may form mapping compounds that may begradually released into the body upon implantation of the presentpost-surgery cavity treatment implant and may form the basis oflymphatic mapping in the future. In this manner, lymphatic mapping maybe carried out immediately after a biopsy procedure via elution of themapping compound (e.g., dyes/pigments and/or radioactive agent)deposited into the collagenous matrix of the implant. In the casewherein a cancer is detected or suspected in the tissue specimenretrieved by the biopsy procedure, this elution of mapping compound fromthe post-biopsy cavity treatment implant may enable the physician toskip the conventional step of injecting dyes/pigments into the patient,which dye/pigment injection step is conventionally carried out prior toa (sentinel) lymph node status evaluation procedure. Embodiments of thepost-biopsy cavity treatment implant according to present invention mayinclude metal-less dyes/pigments as well radiopaque, radioactive orparamagnetic metal-containing dyes/pigments such as, for example,porphyrins and/or porphyrin derivatives (such as chlorophyll and/orchlorophyll derivatives, for example) that are bound to the collagenousmatrix. The porphyrins and/or porphyrin derivatives may be tailored, forexample, to enhance crosslinking and enhance wound healing and/or tocontrol biodegradation, among other reasons. A metal with paramagneticproperties (such as Mn, for example) may be placed within the porphyrinsor porphyrin derivatives so that another mode of recognition may beachieved. Impregnation of the present post-biopsy cavity treatmentimplant with porphyrins or porphyrin derivatives (for example, copperchlorophyllin) gives the post-biopsy cavity treatment implant alymphatic mapping functionality due to the elution of the porphyrins orporphyrin derivatives into the surrounding tissue lymphatic drainagesystem.

According to other embodiments of the present invention, the presentpost-biopsy cavity treatment implants may define or include an internalreservoir configured to contain a volume of a mapping compound and/or abeneficial therapeutic agent. Following the biopsy procedure and thesubsequent implantation of the present post-biopsy cavity treatmentimplant having a predetermined pore architecture into the biopsy cavityand following a histopathology report on the excised biopsy specimen,the physician or RN may pinch or squeeze the post-biopsy cavitytreatment implant to express the mapping compound(s) and/or agent(s)into the surrounding tissue via lymphatic system to the sentinel nodeand other lymphatics. In the absence of such squeezing or pinching, themapping compound and/or therapeutic agent may much more gradually findits way into the surrounding tissue through elution following a gradualbiodegradation of the reservoir.

FIGS. 16-20 are photomicrographs of collagenous matrices having variouspore architectures. As shown, the porosity of the collagenous materialis not formed by bubbles forced through the collagen dispersion prior tolyophilization thereof. Indeed, it is the structure of the collagenmaterial itself that creates and defines the voids or pores (anechoicregions that appear black in the photomicrographs) within the material.FIGS. 17 and 19 show relatively round pores having a wide sizedistribution, whereas FIGS. 16 and 18 show a relatively denser collagenmatrix having a smaller pore size distribution. FIG. 20 shows an exampleof a collagenous matrix that is relatively less dense than, for example,the matrix shown in FIG. 18.

FIGS. 21-23 are combinations of photomicrographs to illustrate furtherembodiments of the post-biopsy cavity treatment implants according tothe present invention. FIG. 21 shows a post-biopsy cavity treatmentimplant 2100 that includes a first portion 2102 having a first porearchitecture and, stacked thereon, a second portion 2104 having a secondpore architecture. As shown, the pore architecture of the first portion2102 may be characterized as being relatively denser than the porearchitecture of the second portion 2104. Alternatively, the post-biopsycavity treatment implant 2100 may be structured such that the firstportion has a higher porosity (is less dense) than that of the secondportion 2104. The thicknesses of the first and second portions 2102,2104 may be varied at will. More than two layers of collagenous materialmay be provided.

FIG. 22 shows a post-biopsy cavity treatment implant 2200 having agraduated porosity profile. Such a post-biopsy cavity treatment implant2200 may be formed by lining up a plurality of collagen matrices havingof progressively lower densities. That is, matrix 2002 has the highestdensity (amount of collagen per unit volume), matrix 2204 has the nexthighest density, matrix 2206 has the next to lowest porosity and matrix2208 has the lowest porosity of the entire post-biopsy cavity treatmentimplant 2200. Alternatively, the degree to which each matrix iscrosslinked may be varied and controlled. For example, each matrix maybe crosslinked to a different degree through the use of, for example,gluteraldehyde. For example, matrix 2202 may be configured to have about0.0085% gluteraldehyde, matrix 2204 may be configured with about 0.0075%gluteraldehyde, matrix 2206 may be configured with about 0.0065%gluteraldehyde and matrix 2208 may be configured with about 0.0055%gluteraldehyde, for example. Other concentrations are possible, as aredifferent reagents. After superimposing all four such matrices 2202,2204, 2206 and 2208, a (in this case, piece-wise linear) cross-linkingand/or porosity gradient may be achieved across the embodiment of thepresent post-biopsy cavity treatment implant shown at 2200.

FIG. 23 shows a composite post-biopsy cavity treatment implant 2300having a more complex structure, according to another embodiment of thepresent invention. The post-biopsy cavity treatment implant 2300includes three distinct collagen matrices, as shown at 2302, 2306 and2308. As shown, each of the matrices 2302, 2306 and 2308 has a uniquepore architecture. Indeed, the portion of the post-biopsy cavitytreatment implant referenced at numeral 2302 has a dense appearance, inwhich the pores have a high aspect ration and are aligned substantiallyparallel to the length of the device 2300. The post-biopsy cavitytreatment implant 2300 also includes a second portion 2304 that includestwo unique collagenous matrices referenced at 2306 and 2308, each havingdifferent pore architectures. Whereas matrix 2306 features a widedistribution of pore shapes and sizes, matrix 2308 featurescomparatively larger, generally rounder pores than those of matrix 2306.Each of these matrices 2302, 2306 and 2308 may have a unique ultrasonicor X-ray signature and/or contain dyes/pigments or radiopaque materialsor compounds. Moreover, not only may the various matrices be visibleunder selected modalities, the interfaces therebetween may also providethe physician with position and orientation information of thepost-biopsy cavity treatment implant within the cavity. Indeed, thereare distinct interfaces between dissimilar materials between matrices2302 and 2306, between matrices 2302 and 2308 as well as a distinctinterface between adjoining matrices 2306 and 2308, each of which may bereadily visible under, for example, ultrasound. It is to be noted thatthe interfaces between the external surfaces of all three matrices 2302,2306 and 2308 with the surrounding tissue may also provide the physicianwith additional visual clues are to the position and orientation of thepost-biopsy cavity treatment implant 2300 within the cavity in which itis implanted. The interfaces described herein, as well as the differentrates of swelling may be achieved through control of the porosity and/oras through the control of crosslinking. A single post-biopsy cavitytreatment implant may include constituent portions controlled to have apredetermined pore architecture and/or predetermined portions havingcontrolled crosslinking. Although the irregular closed features withinthe drawings are intended to suggest pores of various configurations anddensities, they are alternatively intended to indicate crosslinking.Therefore, illustrated differences in these irregular closed featuresbetween adjacent portions of an implant may also be interpreted as beingdifferences in crosslinking densities between adjacent portions in theimplant.

Use of the post-biopsy cavity treatment implants disclosed herein is notlimited to filling post biopsy cavities. Indeed, the present post-biopsycavity treatment implants also find utility in the correction of defectscaused by poorly healed cavities, whatever their origin or cause. Thepresent post-biopsy cavity treatment implants may be placed in cavitiesin which it is desired that the collagen matrices be replaced, overtime, with (human or animal) autogenous tissue. Hence, the embodimentsof the present invention may be used for the repair of tissue that hasbeen damaged due to tissue removal, thereby providing a favorable tissuescaffold in which autogenous tissue may infiltrate and grow. Inaddition, embodiments of the post-biopsy cavity treatment implantsaccording to the present invention may serve to absorb exudates withinthe cavity, thereby further facilitating the healing process.

FIG. 24 shows a post-biopsy cavity treatment implant 2400, according toanother embodiment of the present invention. The post-biopsy (or, moregenerally, post-excisional) implant 2400 includes a radiopaque element2402. The radiopaque element may be formed as a clip, a staple, or mayhave other shapes, as discussed herein below with reference to FIGS. 34,36 and 38-40. The radiopaque element 2402 may also exhibit othercharacteristics, besides its visibility under X-Ray. For example, theelement 2402 may have paramagnetic characteristics, to enable theimplant 2400 to be visible under electron paramagneticresonance-spectroscopy.

Coupled to the radiopaque element 2402 is a core portion 2404. The coreportion 2404 may include a first porous matrix that defines a controlledpore architecture. The pore architecture of the core portion 2404 may becontrolled in a manner similar to that described above. According to anembodiment of the present invention, the core portion 2404 may includeor be formed of, for example, a polylactide (PLA), a polyglycolide(PGA), a poly(lactide-co-glycolide) (PLGA), a polyglyconate, apolyanhydride, PEG, cellulose, a gelatin, a lipid, a polysaccharide, astarch and/or a polyorthoester.

Coupled to the core portion 2404 is a shell portion 2406 that includes asecond porous matrix defining a second controlled pore architecture thatis different from the pore architecture of the core portion 2404.According to an embodiment of the present invention, the shell portion2406 includes collagen. Such a collagenous shell portion 2406 may beselectively configured to have a predetermined pore density, poreshapes, pore sizes and pore orientation, for example. Such controlledpore architecture may influence the degree and the manner in which thecollagenous shell portion 2406 swells when the implant 2400 is placed,immersed or implanted in a biological fluid environment, such as acavity within a patient's body. Such controlled pore architecture alsoinfluences tissue ingrowth, by providing a scaffolding support structureon and within which new tissue may develop. The rate at which the shellportion 2406 degrades within the body may also be influenced bycontrolling the crosslinking of the collagenous matrix of the shellportion 2406. By controlling the formation and the density ofcrosslinks, it is possible to control and/or influence some of themechanical, physicochemical and biological properties of the collagenousshell portion 2406.

Visualization of the post-biopsy cavity treatment implant 2400 isfacilitated not only by the presence of the radiopaque element 2402within the core portion 2404, but also by means of the echogenic natureof the core portion 2404 and of the shell portion 2406. Such dissimilarpore architectures in the core portion 2404 and shell portion 2406 mayalso influence the relative elasticity of the two portions 2404 and 2406further enabling the implant to be visible under elastography.

More than one radiopaque element 2402 may be present in the core portion2404. Moreover, another element exhibiting radiopacity, havingparamagnetic characteristics and/or visible under other modalities (suchas ultrasound, for example), may be present in the core portion 2404and/or the shell portion 2406. At least the shell portion 2406 mayinclude a dye, a pigment, a contrast medium and/or a beneficialtherapeutic agent (for example) disposed therein. Such dye, a pigment, acontrast medium and/or a beneficial therapeutic agent may be heldsponge-like within the porous matrix of the shell portion 2406 anddelivered through elution over time, but may also be contained within aninternal reservoir (a voided space) defined within the core portion 2404and/or the shell portion 2406. For example, the internal reservoir maybe configured to deliver the dye, pigment, contrast medium and/ortherapeutic agent at a first rate when the reservoir is breached and ata second rate that is lower than the first rate when the reservoir isnot breached.

FIG. 25 shows the post-biopsy cavity treatment implant 2400 of FIG. 24loaded into an exemplary introducer 804, according to an embodiment ofthe present invention. The post-biopsy cavity treatment implant 2400, ina pre-implanted state, may be loaded into the introducer 804, which maythen be inserted into the tissue 110 through the access path 127 and atleast partially into the cavity chamber 128 of the cavity 126, in themanner illustrated in FIG. 8. The post-biopsy cavity treatment implant2400 may then be delivered to the cavity 126 and thereafter be left inplace and the introducer 804 withdrawn. The pre-implanted state of thepost-biopsy cavity treatment implant 2400 is preferably in a state inwhich it occupies its minimum volume. According to an embodiment of thepresent invention, the pre-implanted state of the post-biopsy cavitytreatment implant 2400 is a lyophilized (e.g., dehydrated) state and thepost-biopsy cavity treatment implant may be configured to swell whenplaced within a biological fluid environment such as the cavity 126.

FIG. 26 shows a post-biopsy cavity treatment implant 2600 according to astill further embodiment of the present invention, in various stages ofmanufacture. Embodiments of the present post-biopsy cavity treatmentdevice may assume most any shape that is suited to the shape and size ofthe cavity into which it is designed to be placed. One such shape is thegenerally right cylindrical shape (e.g., a disc) shown in FIG. 26. Theimplant 2600, at the top left hand of FIG. 26 is shown in anintermediate manufacturing shape; i.e., prior to assuming its finalpre-implantation shape. The implant 2600 includes a radiopaque element2602 that may be coupled with a core portion 2604. The core portion2404, in FIG. 24, is shaped as a cylinder. However, the shape of thecore portion may be freely selected. In FIGS. 26-27, the core portion2604 has a generally rectangular cross-section. To couple the coreportion 2604 with the shell portion 2606, the core portion 2604 may beplaced on a pedestal within a mold. In the case wherein the shellportion 2606 includes collagen, a collagenous slurry may be poured intothe mold and thereafter lyophilized. Other means and methods formanufacturing the implant 2600 may occur to those of skill in this art.

The implant 2600, according to one embodiment of the present invention,may be folded along a diameter thereof, in such a manner as to form theimplant 2600 shown in the plan view shown in the lower left hand side ofFIG. 26. Thereafter, the implant 2600 may again be folded along foldline 2611, in the manner suggested by arrow 2610 to create the implant2600 shown in the lower right hand side of FIG. 26. Additional foldingmay then be carried out along fold lines 2612, 2614 and 2616 to createan implant 2600 having several layers and a generally wedge shape. Thecore portion 2604, depending upon how the folding has been carried out,may be sandwiched within several layers of the folded shell portion2606. In this state, the implant 2600 may be further compressed anddisposed in an introducer, an example of which is shown in FIG. 27 at804 for eventual implantation within a post-biopsy cavity. It should benoted that the folding need not take place as illustrated in FIG. 26,but may be carried out in a different manner, to achieve a differentultimate shape for the implant 2600. In addition or in place of folding,the implant may also be rolled or crumpled (for example) into itsintended pre-implantation shape.

FIG. 28 shows the post-biopsy cavity treatment implant 2600 of FIGS. 26and 27 during implantation, according to an embodiment of the presentinvention. FIG. 29 shows the post-biopsy cavity treatment implant 2600of FIG. 28 after implantation, illustrating the manner in which theimplant 2600 may expand and/or unfold within the cavity 126 afterimplantation, according to an embodiment of the present invention. Asshown, the introducer 804 may be inserted into the tissue through theaccess path 127 and at least partially into the cavity chamber 128 ofthe cavity 126. The post-biopsy cavity treatment implant 2600 may thenbe delivered to the cavity 126 and thereafter be left in place and theintroducer 804 withdrawn. The pre-implanted state of the post-biopsycavity treatment implant 2600 is preferably in a state in which thepost-biopsy cavity treatment implant 2600 occupies its minimum volume.According to an embodiment of the present invention, the pre-implantedstate of the post-biopsy cavity treatment implant 2600 is a lyophilized(e.g., dehydrated) state and the post-biopsy cavity treatment implant2600 may be configured to swell when placed within a biological fluidenvironment such as the cavity 126. Whereas FIG. 28 shows the presentpost-biopsy cavity treatment implant 2600 immediately after implantationin tissue (i.e., still in a state in which it occupies its minimumvolume), FIG. 29 shows the state of the present post-biopsy cavitytreatment implant 2600 a period of time after implantation. As shown,the post-biopsy cavity treatment implant 2600 is no longer in itspre-implanted state. Indeed, the post-biopsy cavity treatment implant2600 having been placed in a biological fluid environment (such as thepatient's tissue), begins to swell. To accelerate the swelling, thesurgeon may inject fluids after placing the device with the intent to“wet” the present post-cavity treatment implant 2600. Substances such assaline, fibrin solution or other catalyst or activator may be used forthat purpose. For example, as part of the insertion device (such as, forexample, the introducer 804), an integral vial may be crushed by thesurgeon to release the activating fluid (for example, an aqueoussolution, dye/pigment) within the cavity 126, thus causing rapidswelling of the implant 2600. Alternately, and as shown in FIG. 9, theintroducer 804 may define an internal lumen 811 over its length and mayinclude a fluid injection port 812 at the proximal end of the device.Fluids such as the aforementioned saline or fibrin may then beintroduced into the cavity 126 through the fluid injection port 812 andthe internal lumen 811 to cause the rapid swelling of the implant 2600or for any other reason. Delivering such fluids can be especially usefulif the field within the cavity 126 is relatively dry as can occur in theideal case.

As the post-biopsy cavity treatment implant 2600 swells, it preferablyswells from a shape in which it is easily implantable through the accesspath 127 to a shape and size wherein it no longer fits through theaccess path 127. As this swelling occurs rapidly after the post-biopsycavity treatment implant 2600 comes into contact with the fluids presentwithin the cavity 126, the surgeon may retract the introducer 804 fromthe cavity 126, close the initial incision and be confident that thepost-biopsy cavity treatment implant 2600 has remain in its intendedposition, squarely within the cavity chamber 128 of the cavity 126, andhas not migrated back into the access path 127.

As shown in FIG. 29, the release of the implant 2600 from compression atit is ejected from the introducer 804, combined with the hydration andsubsequent swelling of the post-biopsy cavity treatment implant 2600within the cavity 126 causes the implant 2600 to at least partiallyunfold (and/or unroll), thereby causing the volume that it occupies toincrease. This unfolding and swelling may enable the implant 2600 tooccupy a significant portion of the internal volume of the cavity 126.This, in turn, aids in promoting tissue ingrowth by providingscaffolding upon and within which new tissue may develop. Moreover, thenow at least partially filled cavity 126 is readily visible under avariety of imaging modalities. As the ranges at which the core and shellportions may biodegrade may be controlled as detailed above, it ispossible to manufacture the implant 2600 to have a predictable rate ofbiodegradation. After the core and shell portions of the implant havesubstantially degraded within the cavity, the radiopaque element willremain in the newly formed tissue within the cavity, providing a readypositional reference of the cavity 126, should that be subsequentlynecessary. More that one such implant 2600 may be placed within thecavity 126.

FIG. 30 shows a post-biopsy cavity treatment implant 3000 according toanother embodiment of the present invention, in various stages ofmanufacture. The implant 3000 is similar to that shown in FIGS. 26-29,but for the presence of two core portions 3004, 3008 within the shellportion 3010. Each of the core portions 3004, 3008 surrounds aradiopaque element 3002, 3306, respectively. To form the implant 3000 inits ultimate pre-implantation shape (i.e., its shape prior to beingplaced in a biological fluid environment), the implant 3000 may first befolded along a diameter thereof, to achieve the shape thereof shown inthe plan view in the lower left hand of FIG. 30. Thereafter, the implant3000 may be sequentially folded along the direction indicated by arrows3010 along the fold lines 3014, 3016, 3018 and 3020 to achieve agenerally wedge shape.

It is to be noted that embodiments of the present post-biopsy cavitytreatment devices are not limited to the shapes described andillustrated herein. Moreover, the present implants may be foldeddifferently than shown, as they may be irregularly folded, rolled orotherwise caused to assume as small a volume as practicable. A greaternumber of core portions may be accommodated within the shell portion3010. Other variations may occur to those of skill in this area, and allsuch variations are believed to fall within the scope of the presentinvention. FIG. 31 shows the post-biopsy cavity treatment implant 3000of FIG. 30 loaded into an exemplary introducer 3022, according toanother embodiment of the present invention.

FIG. 32 shows a post-biopsy cavity treatment implant 3000 according toyet another embodiment of the present invention, in a configurationprior to folding and/or compression. As shown, the post-biopsy cavitytreatment implant 3000 may be shaped, for example, such that the shellportion 3010 is shaped as a rectangular sheet. The embodiment shown inFIG. 32 includes two radiopaque elements 3002 and 3006, although alesser or greater number of such radiopaque elements may be present.Coupled to the radiopaque element 3002 is a core portion 3004 andcoupled to the radiopaque element 3006 is another core portion 3008. Inthe illustrated embodiment, the core portion 3004 surrounds theradiopaque element 3002, the core portion 3008 surrounds the radiopaqueelement 3006 and the shell portion 3010 surrounds both core portions3004 and 3008. Other arrangements of the constituent elements of thepost-biopsy cavity treatment implant 3000 are possible.

According to one embodiment, the post-biopsy cavity treatment implant3000 of FIG. 32 may be folded and/or rolled or otherwise arranged intoany desired shape. FIG. 33 shows the post-biopsy cavity treatmentimplant 3200 of FIG. 32 in one such many possible folded configurations,according to still another embodiment of the present invention. Afterlyophilization, the implant 3200 may be folded two or more times (forexample) and compressed into an introducer, such as shown in FIG. 27 or31. Any folding pattern may be used. Some of the goals of such folding,rolling and/or compression include reducing the dimensions of theimplant 3200, fitting the shape of the implant 3200 to the shape anddimensions of the cavity into which the implant is to be placed, and toinfluence the manner in which the implant unfolds and/or unrolls withinthe cavity, upon being released from the introducer, decompressing andswelling with biological fluids within the environment of use within thepatient. FIG. 33 is to be considered only as illustrative of one of manypossible configurations for the implant 3200.

FIG. 34 shows a core portion 3400 suitable for use in conjunction withthe present post-biopsy cavity treatment implant, according to anotherembodiment of the present invention. As shown, the core portion of thepresent post-biopsy cavity treatment implant need not be rectangular orcylindrical. In the embodiment of FIG. 34, although the core portion3404 has a uniform cylindrical cross-section, it may exhibit a morecomplex geometry. For example, the center portion of the core portion3403 may be locally thinner than the ends thereof. This locally thinnerportion facilitates any folding or rolling that may be carried out tobring the implant into its final (pre-implantation) shape andconfiguration. The core portion 3404 may be coupled to (or surround, asshown in FIG. 34) one or more radiopaque elements 3402. FIG. 35 shows apost-biopsy cavity treatment implant 3500 incorporating the core portion3404 of FIG. 34, according to yet another embodiment of the presentinvention, in a configuration prior to folding and/or compression. Theshell portion 3406 is coupled to the core portion 3403. As shown in FIG.35, the shell portion 3406 may surround the core portion 3404. Theimplant 3500 may then be folded, rolled and/or compressed, as describedabove.

FIG. 36 shows further core portions 3604, 3608 suitable for use inconjunction with the present post-biopsy cavity treatment implant,according to another embodiment of the present invention. FIG. 37 showsa post-biopsy cavity treatment implant 3700 incorporating the coreportions 3604, 3608 of FIG. 36, according to a further embodiment of thepresent invention, in a configuration prior to folding and/orcompression. As shown in FIGS. 36 and 37, more than one core portion maybe coupled to the shell portion 3406 and each (or only one) of such coreportions 3604, 3608 may be coupled to (or surround) a radiopaqueelement, as shown at reference numerals 3602 and 3606. The core portionor portions of a post-biopsy cavity treatment implant according to anembodiment of the present invention may be fabricated in most any shapethat is consistent with the cavity treatment goals. FIG. 38 shows a coreportion 3804 having yet another possible shape. As with the coreportions discussed herein, the core portion 3804 is coupled to orsurrounds a radiopaque element 3802. The core portions shown in FIGS.34-38 may be stamped from a sheet of core material. The core material,according to an embodiment of the present invention, may be formed of orinclude one or more of the following materials: a polylactide (PLA), apolyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), apolyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipid, apolysaccharide, a starch and a polyorthoesters, for example.

FIGS. 39 and 40 shows exemplary radiopaque elements 3900 and 4000suitable for use in conjunction with the present post-biopsy cavitytreatment implant, according to still further embodiments of the presentinvention. The radiopaque element may be shaped as a staple or theletter “C” as shown in FIG. 38 or in another shape, such as shown inFIG. 39, in which the radiopaque element 400 has the general shape ofthe letter “R”. Other shapes and configurations are possible.

FIG. 41 shows a post-biopsy cavity treatment implant 4100, according toa further embodiment of the present invention, in a configuration priorto folding and/or compression. A radiopaque element 4102 is coupled to(or surrounded by) a core portion 4104. In turn, the core portion 4104is coupled to (or surrounded by) a shell portion 4106. This embodimentis similar to that shown in FIG. 26, but for the radial cuts 4108 in theshell portion 4106. The radial cuts 4108 may enable the implant 4100 tobetter accommodate and fill irregularly shaped cavities when the implantis placed in a biological fluid environment and the implant 4100decompresses, unfolds or unrolls and swells. Such radial cuts define aplurality of independently movable free ends 4110 in the peripheralportion of the implant 4100.

FIG. 42 shows a post-biopsy cavity treatment implant 4200, according toanother embodiment of the present invention, in a configuration prior tofolding and/or compression. A radiopaque element 4202 is coupled to (orsurrounded by) a core portion 4204, as shown in the cutout (the purposeof the cutout is only to show the internal structure of the implant 4200and is not present in the actual implant). In turn, the core portion4204 is coupled to (or surrounded by) a shell portion 4206. Thisembodiment is similar to that shown in FIG. 13E. The implant 4200includes a radiopaque element 4202 coupled to or surrounded by a coreportion 4204 that is, in turn, coupled to or surrounded by a shellportion 4206. The core portion 4204 and the radiopaque element may beconfigured and/or have any of the characteristics discussed above andshown in the corresponding figures. The shell portion 4206, as shown,defines a center portion 4208 and a peripheral portion and wherein theperipheral portion defines a plurality of independently movable freeends 4210.

While the foregoing detailed description has described preferredembodiments of the present invention, it is to be understood that theabove description is illustrative only and not limiting of the disclosedinvention. For example, the post-biopsy cavity treatment implantsdisclosed herein may be configured to have a unique “signaturing”capability, in which a specific code appears under a given imagingmodality. The specific code may be formed within or molded into thestructure of the collagen matrix or matrices. For example, a combinationof the elements with different crosslinking patterns (e.g., bundles ofcylindrical fibers or layers of collagen sponges) may be used for bothpattern recognition and predictable filling of the post biopsy procedurecavity. Alternatively, the code may be embodied as a discrete echogenicor radiopaque constituent element of the implant. The codes may conferinformation to the radiologist or treating physician when viewed underX-ray or ultrasound. Alternatively still, the post-biopsy cavitytreatment implants having predetermined pore architectures and/orcontrolled crosslinking densities according to the disclosed embodimentsmay include a biocompatibly-sealed integrated circuit that may beinterrogated electronically to convey information to the physician.Those of skill in this art may recognize other alternative embodimentsand all such alternative embodiments are deemed to fall within the scopeof the present invention.

1. A method of treating a cavity created by a percutaneous excisionalprocedure carried out through an incision, comprising the steps of:providing a post-procedure cavity implant, the post-procedure cavityimplant including: a radiopaque element; a core portion coupled to theradiopaque element, the core portion including a first porous matrixdefining a first controlled pore architecture, and a shell portioncoupled to the core portion, the shell portion including a second porousmatrix defining a second controlled pore architecture that is differentfrom the first controlled pore architecture; implanting thepost-procedure cavity implant into the cavity, and closing the incision.2. The method of claim 1, wherein the providing step is carried out withthe core portion surrounding the radiopaque element.
 3. The method ofclaim 1, wherein the providing step is carried out with the shellportion surrounding the core portion.
 4. The method of claim 1, whereinthe providing step is carried out with the core portion surrounding theradiopaque element and the shell portion surrounding the core portion.5. The method of claim 1, wherein the providing step is carried out withthe shell portion swelling faster than the core portion when the implantis placed in a biological fluid environment.
 6. The method of claim 1,wherein the providing step is carried out with the shell portionswelling to a greater extent than the core portion when the implant isplaced in a biological fluid environment.
 7. The method of claim 1,wherein the providing step is carried out with the first controlled porearchitecture differing from the second controlled pore architecture withrespect to at least one of: pore density, pore shape, pore orientationand pore dimensions.
 8. The method of claim 1, wherein the providingstep is carried out with the radiopaque element including a portionhaving a paramagnetic property.
 9. The method of claim 1, wherein theproviding step is carried out with at least one of the core and shellportions including a dye disposed therein.
 10. The method of claim 1,wherein the providing step is carried out with at least one of the coreand shell portions including a pigment disposed therein.
 11. The methodof claim 1, wherein the providing step is carried out with at least oneof the core and shell portions including a contrast medium disposedtherein.
 12. The method of claim 1, wherein the providing step iscarried out with at least one of the core and shell portions including atherapeutic agent disposed therein.
 13. The method of claim 1, whereinthe providing step is carried out with at least one of the core andshell portions being biodegradable.
 14. The method of claim 1, whereinthe providing step is carried out with at least the shell portionincluding collagen.
 15. The method of claim 1, wherein the providingstep is carried out with the core portion including at least one of apolylactide (PLA), a polyglycolide (PGA), a poly(lactide-co-glycolide)(PLGA), a polyglyconate, a polyanhydride, PEG, cellulose, a gelatin, alipid, a polysaccharide, a starch and a polyorthoester.
 16. The methodof claim 1, wherein the providing step is carried out with the core andshell portions being configured so as to form a laminar structure. 17.The method of claim 1, wherein the providing step is carried out with atleast one of the core and shell portions being echogenic.
 18. The methodof claim 1, wherein the providing step is carried out with at least theshell portion including a plurality of fibers.
 19. The method of claim1, wherein the providing step is carried out with at least one of thecore and shell portions including an internal reservoir configured tocontain at least one of a dye, a pigment and a therapeutic agent. 20.The method of claim 19, wherein the providing step is carried out withthe internal reservoir being configured to deliver the at least one ofdye, pigment and therapeutic agent through elution when the implant isplaced in a biological fluid environment.
 21. The method of claim 19,wherein the providing step is carried out with the internal reservoirbeing configured to deliver the at least one of dye, pigment andtherapeutic agent at a first rate when the reservoir is breached and ata second rate that is lower than the first rate when the reservoir isnot breached.
 22. The method of claim 1, wherein the providing step iscarried out with the shell portion being configured to swell to agreater degree than the core portion when the implant is placed in thebiological fluid environment.
 23. The method of claim 1, wherein theproviding step is carried out with the shell portion including collagenand wherein the providing step is carried out with a crosslinkingdensity of the shell portion is controlled through adding a selectedamount of a bifunctional reagent to the collagen.
 24. The method ofclaim 23, wherein the providing step is carried out with thebifunctional reagent including at least one of an aldehyde and acyanamide.
 25. The method of claim 24, wherein the providing step iscarried out with the aldehyde including a glutaraldehyde.
 26. The methodof claim 1, wherein the providing step is carried out with the shellportion including collagen and wherein the providing step is carried outwith a crosslinking density of the shell portion is controlled by anapplication of energy to the collagen.
 27. The method of claim 26,wherein the providing step is carried out with the application of energyincluding at least one of dehydrothermal processing, exposure to UVlight and radiation.
 28. The method of claim 1, wherein the providingstep is carried out with the shell portion including collagen andwherein the providing step is carried out with a crosslinking density ofthe shell portion being controlled by a combination of dehydrothermalprocessing and exposure to cyanamide.
 29. The method of claim 1, whereinthe providing step is carried out with the implant, in a state prior tobeing placed in a biological fluid environment, being generallywedge-shaped.
 30. The method of claim 1, wherein the providing step iscarried out with the implant, in a state prior to being placed in abiological fluid environment, having a shape of a disk that has beenfolded multiple times.
 31. The method of claim 1, wherein the providingstep is carried out with the implant, in a state prior to being placedin a biological fluid environment, having a rectangular shape.
 32. Themethod of claim 1, wherein the providing step is carried out with theshell portion defining a center portion and a peripheral portion andwherein the providing step is carried out with the peripheral portiondefines a plurality of independently movable free ends.
 33. The methodof claim 1, wherein the providing step is carried out with at least oneof the core portion and the shell portion including a radioactivematerial.
 34. The method of claim 9, wherein the dye is radioactive. 35.The method of claim 10, wherein the pigment is radioactive.
 36. A methodof treating a cavity created by an excisional procedure, comprising thesteps of: selecting a first biodegradation rate range; selecting asecond biodegradation rate range that is different from the firstbiodegradation rate range; providing a post-procedure cavity implant,the post-procedure cavity implant including: a radiopaque element; acore portion coupled to the radiopaque element, the core portion beingconfigured to biodegrade at a first effective rate within the firstbiodegradation rate range, and a shell portion coupled to the coreportion, the shell portion being configured to biodegrade at a secondeffective rate within the second biodegradation rate range, andimplanting the post-procedure cavity implant within the cavity.
 37. Themethod of claim 36, wherein the providing step is carried out with thecore portion surrounding the radiopaque element.
 38. The method of claim36, wherein the providing step is carried out with the shell portionsurrounding the core portion.
 39. The method of claim 36, wherein theproviding step is carried out with the core portion surrounding theradiopaque element and the shell portion surrounding the core portion.40. The method of claim 36, wherein the providing step is carried outwith the shell portion swelling faster than the core portion when theimplant is placed in a biological fluid environment.
 41. The method ofclaim 36, wherein the providing step is carried out with the shellportion swelling to a greater extent than the core portion when theimplant is placed in a biological fluid environment.
 42. The method ofclaim 36, wherein the providing step is carried out with the firstcontrolled pore architecture differing from the second controlled porearchitecture with respect to at least one of: pore density, pore shape,pore orientation and pore dimensions.
 43. The method of claim 36,wherein the providing step is carried out with the radiopaque elementincluding a portion having a paramagnetic property.
 44. The method ofclaim 36, wherein the providing step is carried out with at least one ofthe core and shell portions including a dye disposed therein.
 45. Themethod of claim 36, wherein the providing step is carried out with atleast one of the core and shell portions including a pigment disposedtherein.
 46. The method of claim 36, wherein the providing step iscarried out with at least one of the core and shell portions including acontrast medium disposed therein.
 47. The method of claim 36, whereinthe providing step is carried out with at least one of the core andshell portions including a therapeutic agent disposed therein.
 48. Themethod of claim 36, wherein the providing step is carried out with atleast one of the core and shell portions being biodegradable.
 49. Themethod of claim 36, wherein the providing step is carried out with atleast the shell portion including collagen.
 50. The method of claim 36,wherein the providing step is carried out with the core portionincluding at least one of a polylactide (PLA), a polyglycolide (PGA), apoly(lactide-co-glycolide) (PLGA), a polyglyconate, a polyanhydride,PEG, cellulose, a gelatin, a lipid, a polysaccharide, a starch and apolyorthoester.
 51. The method of claim 36, wherein the providing stepis carried out with the core and shell portions being configured so asto form a laminar structure.
 52. The method of claim 36, wherein theproviding step is carried out with at least one of the core and shellportions being echogenic.
 53. The method of claim 36, wherein theproviding step is carried out with at least the shell portion includinga plurality of fibers.
 54. The method of claim 36, wherein the providingstep is carried out with at least one of the core and shell portionsincluding an internal reservoir configured to contain at least one of adye, a pigment and a therapeutic agent.
 55. The method of claim 54,wherein the providing step is carried out with the internal reservoirbeing configured to deliver the at least one of dye, pigment andtherapeutic agent through elution when the implant is placed in abiological fluid environment.
 56. The method of claim 54, wherein theproviding step is carried out with the internal reservoir beingconfigured to deliver the at least one of dye, pigment and therapeuticagent at a first rate when the reservoir is breached and at a secondrate that is lower than the first rate when the reservoir is notbreached.
 57. The method of claim 36, wherein the providing step iscarried out with the shell portion being configured to swell to agreater degree than the core portion when the implant is placed in thebiological fluid environment.
 58. The method of claim 36, wherein theproviding step is carried out with the shell portion including collagenand wherein the providing step is carried out with a crosslinkingdensity of the shell portion is controlled through adding a selectedamount of a bifunctional reagent to the collagen.
 59. The method ofclaim 54, wherein the providing step is carried out with thebifunctional reagent including at least one of an aldehyde and acyanamide.
 60. The method of claim 59, wherein the providing step iscarried out with the aldehyde including a glutaraldehyde.
 61. The methodof claim 36, wherein the providing step is carried out with the shellportion including collagen and wherein the providing step is carried outwith a crosslinking density of the shell portion is controlled by anapplication of energy to the collagen.
 62. The method of claim 61,wherein the providing step is carried out with the application of energyincluding at least one of dehydrothermal processing, exposure to UVlight and radiation.
 63. The method of claim 36, wherein the providingstep is carried out with the shell portion including collagen andwherein the providing step is carried out with a crosslinking density ofthe shell portion being controlled by a combination of dehydrothermalprocessing and exposure to cyanamide.
 64. The method of claim 36,wherein the providing step is carried out with the implant, in a stateprior to being placed in a biological fluid environment, being generallywedge-shaped.
 65. The method of claim 36, wherein the providing step iscarried out with the implant, in a state prior to being placed in abiological fluid environment, having a shape of a disk that has beenfolded multiple times.
 66. The method of claim 36, wherein the providingstep is carried out with the implant, in a state prior to being placedin a biological fluid environment, having a rectangular shape.
 67. Themethod of claim 36, wherein the providing step is carried out with theshell portion defining a center portion and a peripheral portion andwherein the providing step is carried out with the peripheral portiondefines a plurality of independently movable free ends.
 68. The methodof claim 36, wherein the providing step is carried out with at least oneof the core portion and the shell portion including a radioactivematerial.
 69. The method of claim 40, wherein the dye is radioactive.70. The method of claim 41, wherein the pigment is radioactive.